The major protein and glycoprotein antigens of Treponema pallidum, Nichols strain, will be identified by polyacrylamide gel electrophoresis, Western blotting and gel immunoreactivity (GIRA) techniques, and immunoprecipitation of antigens with multivalent antisera and monoclonal antibodies. The antigenic structure of the Nichols strain will be compared to that of several nonpathogenic treponemes as well as pathogens including T. pertenue and "street strains" of T. pallidum. The major antigens of T. pallidum, Nichols strain, will be isolated and partially purified. The immunologic responses of infected rabbits and humans to each of these antigens will be evaluated by serologic testing as well as by lymphocyte transformation, lymphokine release, neutralization, and opsonization assays. Following immunization of rabbits with the isolated antigens, humoral and cellular responses of the artifically immunized animals will be measured by the assays described above. In addition, these immunized animals will be challenged with virulent T. pallidum in order to assess the degree of protection conferred by the individual antigens. It is anticipated that these studies will provide a better understanding of the pathogenesis of syphilis and may lead to the identification of antigens which could serve as the basis for more specific serodiagnostic tests and, ultimately, the development of effective immunization procedures.